DIADENOSINE TETRAPHOSPHATE-INDUCED INHIBITION OF ATP-SENSITIVE K+ CHANNELS IN PATCHES EXCISED FROM VENTRICULAR MYOCYTES

Diadenosine 5',5 ''-P-1,P-4-tetraphosphate (Ap(4)A) has been termed 'a larmone' due to its role in intracellular signaling during metabolic s tress. It is not known whether Ap,A could modulate ATP-sensitive K+ (K -ATP) channels, a family of channels regulated by the metabolic status of a cell. We applied the single-channel patch-clamp technique to mea sure the effect of Ap(4)A on K-ATP channels. When applied to the intra cellular side of patches, excised from guinea-pig ventricular myocytes , Ap(4)A inhibited K-ATP channel activity, in a reversible and concent ration-dependent (half-maximal concentration similar to 17 mu M) manne r. We conclude that Ap(4)A, a naturally occurring diadenosine polyphos phate, is actually an inhibitor of the myocardial K-ATP channel.